What does the ICH E6(R3) mean for clinical trial data archiving?

Recently, the ICH released a new draft of the ICH E6 (R3) guidelines. And while the finalised version is set for release at the end of 2023, we can see what is expected to be published.

For context, ICH stands for International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. This international council is a collaborative effort between regulatory authorities and the pharmaceutical industry. Their purpose is to discuss scientific and technical matters related to the development and registration of pharmaceutical products.

The ICH E6 (R3) guidelines details the responsibilities of those involved in clinical trials to ensure the safe running and compliance of the trial.

In this blog post, I will be highlighting some key areas related to the retention of data covered within these guidelines.

3.16.1 (e)The sponsor should ensure that documented processes are implemented to ensure the data integrity for the full data life cycle.

For the full data life cycle – beyond trial closure – into archival, there must be documented processes to ensure data integrity. What are documented processes in regard to archival?

Procedures, SOPs, and/or guidelines

To break this down further, the full data life cycle extends to the required period whereby data is to be disposed (after the retention period). For example, in EU regulation requirements, this extends to 25 years after the trial has concluded. The main concern is ensuring data integrity for this entire period.

This section is referencing for documented processes to be implemented, indicating that defined procedures are to be undertaken. Whether these are written as standards operating procedures (SOPs) or other guidance documents, these must be documented and remain accessible.

These documented processes also must outline how the integrity of the data is to be maintained. For maintaining data beyond clinical trial conclusion, we have an eBook guiding on how this can be achieved. 

3.16.1 (g) The sponsor should provide guidance to investigators/institutions, service providers and trial participants, where relevant, on the expectations for data capture, data changes, data retention and data disposal

This can mean two things, firstly, the sponsor holds the responsibility to understand and define the expectations for data capture, changes, retention and disposal. . It is important here to be aware of the requirements for data handling based on the relevant authorities. For example, for clinical trials operating in the EU, participant data is to be retained for a minimum of 25 years. Whereas clinical trials in the US, the retention period varies from a minimum of 2 years and depends on the type of data produced. Furthermore, the MHRA requires data to be retained for a minimum of 5 years.

Secondly, it is the sponsors’ responsibility to communicate such expectations to the outlined parties.  These data expectations need to be defined and then this be communicated to the trial participants as well as the party involved in retaining the data.

3.16.1 (u)The sponsor should ensure that trial data are protected from unauthorised access, disclosure, dissemination or alteration and from inappropriate destruction or accidental loss.

Here, it is referring to the responsibility of the sponsor to ensure that data protected from any activity that can risk its integrity. This includes safeguarding against data loss, corruption, unauthorised access, disclosure, dissemination or alteration.

What is not explicitly mentioned here, but is reflected amongst the guidelines as a whole, is that this management of data goes beyond trial closure. The data lifecycle depends on the relevant regulatory body but ends at the destruction of data past the retention period.

As such, the safeguarding of data from the defined above risks, extends beyond trial closure and into data retention periods. Overall, it is the sponsor’s responsibility to ensure the safeguarding throughout this period.

3.16.3 (a) The sponsor (or subsequent owners of the data) should retain all of the sponsor-specific essential records pertaining to the trial in conformance with the applicable regulatory requirement(s).

The emphasis here is placed on the sponsor’s responsibility (or anyone who takes ownership of the data in future) to retain their specific records relating to the trial. Retaining the data must be done in accordance with applicable regulatory requirements. For example, sponsors adhering to EU Regulation 536 are required to retain clinical trial data for 25 years.

The action of retaining data is unfortunately not as simple as placing it in a box and leaving it until its required. Retention under regulation means to ensure the completeness, accessibility and readability of records throughout the retention period. The responsibility of this ultimately falls on the sponsor.

3.16.3 (b) The sponsor should inform the investigator(s)/institution(s) and service providers, when appropriate, in writing of the need for essential records retention and should notify the investigator(s)/institution(s) and service providers, when appropriate, in writing when the trial-related records are no longer needed.

There are two key responsibilities for the sponsor highlighted here:

1. To inform the investigator/institution and service provider around the retention needs for the data. This implies that the sponsor is responsible for the awareness of retention periods for essential records and that they are to inform all relevant parties about this. It’s further required that this is to be done in writing, this establishes a clear and documented understanding of the need for record retention.
2. To notify the investigator/institution and service provider in writing when trial-related data is no longer needed. This is in addition to the first point to ensure clear communication around retention obligations. This part, however, ensures that unnecessary retention of data is avoided and therefore streamlines the retention process whilst remaining in compliance.

3.16.3 (c) The sponsor should report any transfer of ownership of the essential records to the appropriate authority(ies) as required by the applicable regulatory requirement(s).

For instance, say the drug in question is being purchased by another pharmaceutical company, all the clinical trial data must be transferred to the new owner. This clause requires sponsors to also report this transfer of ownership to the applicable authorities.

This reporting of ownership would also need to be followed if data is transferred over to a third-party dedicated archive.

Overall, this clause is to ensure clear and documented record trails are established regarding the ownership of essential documents. Therefore, authorities can maintain oversight and access to these trial records if needed.

3.16.4 (a) The sponsor should ensure that it is specified in the protocol or other documented agreement that the investigator(s)/institution(s) provide direct access to source records for trial-related monitoring, audits, IRB/IEC review and regulatory inspection.

This statement is emphasising the responsibility of the sponsor to ensure that the protocol or other documented agreement clearly specifies that the investigator/institution must provide direct access to original records as described (relating to the monitoring, audits IRB/IEC review and regulatory inspection).

This means that the sponsor has to consider specific language in the trial protocol or other written agreements that mandates the investigator/institution to grant such access. Following this guideline allows for transparency, quality control and regulatory supervision. In doing so, it ensures that authorised parties have unrestricted access to the original records to evaluate the integrity, validity and compliance of the trial.

In Summary…

The guidelines we have highlighted here emphasise the need for stringent processes and strong communication to ultimately provide a safe and secure long-term data management. The sponsor of the clinical trial is defined as responsible for ensuring these processes and communication overall. What’s more, these guidelines do not cover a specific set of regulation but instead attempts to tie together multiple pieces of regulations. That being said, it is important for sponsors to be aware of the regulatory body that is relevant to their own clinical trial and to implement this piece of guidance in accordance with these standards.

Data integrity remains a critical aspect of the data related sections of these guidelines. These guidelines require processes for protecting data from risks that could otherwise damage the integrity of data.

The key takeaways from this post include:

• The sponsor is defined as responsible for the activities highlighted.
• The sponsor is responsible for ensuring data integrity is maintained for the full life cycle of clinical data (which extends beyond trial completion).
• The sponsor must communicate expectations of data capture, changes, retention and disposal to relevant stakeholders.
• It is the sponsor’s responsibility to understand the data handling expectations.
• The sponsor must retain their specific records relating to the trial in accordance to retention requirements and is responsible for ensuring correct disposal of related records.
• If transfer of data is needed, the sponsor must record and report this to authorities.
• The sponsor must ensure clear communicated guidance is given to the institution/investigator for direct access to records.